ABCMdb

PMID: 22859523

Quinton P, Molyneux L, Ip W, Dupuis A, Avolio J, Tullis E, Conrad D, Shamsuddin AK, Durie P, Gonska T
beta-Adrenergic Sweat Secretion as a Diagnostic Test for Cystic Fibrosis.
Am J Respir Crit Care Med. 2012 Oct 15;186(8):732-9. doi: 10.1164/rccm.201205-0922OC. Epub 2012 Aug 2., [PubMed]

Sentences

No. Mutations Sentence Comment

42 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg1162* ABCC7 p.Leu206Trp ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Arg764* ABCC7 p.Arg117Cys ABCC7 p.Trp216Cys DIAGNOSTIC CHARACTERISTICS OF PARTICIPANTS IN THE VALIDATION COHORT Group Age (yr) Sex Genotype Sweat Cl2 (mmol/L) Cholinergic b-Adrenergic Ratio b/Chol Healthy 38 M 2/2 15 64.45 72.79 1.13 Healthy 39 M 2/2 18 81.61 86.08 1.05 Healthy 54 F 2/2 29 48.90 47.30 0.97 Healthy 64 F 2/2 28 50.64 57.54 1.14 Healthy 54 F 2/2 11 68.63 52.30 0.76 Hetero. 64 M F508del/2 16 68.21 36.78 0.54 Hetero. 56 M F508del/2 53 82.44 59.57 0.72 Hetero. 27 F F508del/2 11 78.30 46.30 0.59 Hetero. 29 F F508del/2 16 65.63 26.13 0.40 Hetero. 51 F G551D/2 62 39.13 16.50 0.42 CFTR-RD CBAVD 41 M W1282X/5T 55 84.61 20.69 20.01 CFTR-RD CBAVD 52 M F508del/R117H (7T) 57 70.39 20.61 20.01 CFTR-RD CBAVD 41 M F508del/5T 40 68.00 22.29 20.03 CFTR-RD CBAVD 47 M G551D/R117H (7T) 57 65.93 10.08 0.15 CFTR-RD CBAVD 40 M L206W/W216C 42 67.80 17.00 0.25 CFTR-RD CBAVD 26 M 36599delC15T/7T 55 91.55 0.18 0.00 CFTR-RD Sinopulm 65 F F508del/c.876-9_876-6delGATT 51 74.30 32.20 0.43 CFTR-RD Sinopulm 39 F R764X/2 12 24.64 3.49 0.14 CFTR-RD Sinopulm 17 F 5T/2 50 52.95 14.24 0.27 CFPS 21 M F508del/2 97 46.19 0.56 0.01 CFPS 33 M F508del/3849110kbC.T 50 76.22 22.94 20.04 CFPS 58 M 71111G.T/A455E 72 70.19 23.06 20.04 CFPS 41 M G551D/3849110kbC.T 88 87.37 0.08 0.00 CFPS 54 F F508del/R117C 59 36.74 1.06 0.03 CFPS 23 F F508del/A455E 82 64.85 3.46 0.05 CFPS 30 F D1152H/D1152H 31 41.52 23.54 20.09 CFPS 55 F G551D/2 99 67.62 21.78 20.03 CFPS 42 F F508del/1002-2A.G 94 27.64 2.63 0.10 CFPS 46 F 3849110kbC.T/3849110kbC.T 53 24.43 21.16 20.05 CFPS 14 F R1162X/3849110kbC.T 46 50.19 20.49 20.01 CFPI 32 M F508del/F508del 108 73.93 1.41 0.02 CFPI 28 M F508del/F508del 84 95.13 3.45 0.04 CFPI 24 F F508del/F508del 109 60.48 4.06 0.07 CFPI 34 F F508del/F508del 115 79.24 0.99 0.01 CFPI 35 F F508del/F508del 87 79.79 23.02 20.04 CFPI 44 F F508del/F508del 112 80.60 1.23 0.02 CFPI 23 F F508del/G551D 90 45.80 0.80 0.02 Definition of abbreviations: CBAVD ¼ congenital bilateral absence of vas deference; CF ¼ cystic fibrosis; CFPI ¼ pancreatic-insufficient patients with CF; CFPS ¼ pancreatic-sufficient patients with CF; CFTR ¼ CF transmembrane regulator; CFTR-RD ¼ CFTR-related disorder; hetero ¼ heterozygotes; sinopulm ¼ chronic sinopulmonary disease. Login to comment 43 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Arg1162* ABCC7 p.Leu206Trp ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Arg764* ABCC7 p.Arg117Cys ABCC7 p.Trp216Cys DIAGNOSTIC CHARACTERISTICS OF PARTICIPANTS IN THE VALIDATION COHORT Group Age (yr) Sex Genotype Sweat Cl2 (mmol/L) Cholinergic b-Adrenergic Ratio b/Chol Healthy 38 M 2/2 15 64.45 72.79 1.13 Healthy 39 M 2/2 18 81.61 86.08 1.05 Healthy 54 F 2/2 29 48.90 47.30 0.97 Healthy 64 F 2/2 28 50.64 57.54 1.14 Healthy 54 F 2/2 11 68.63 52.30 0.76 Hetero. 64 M F508del/2 16 68.21 36.78 0.54 Hetero. 56 M F508del/2 53 82.44 59.57 0.72 Hetero. 27 F F508del/2 11 78.30 46.30 0.59 Hetero. 29 F F508del/2 16 65.63 26.13 0.40 Hetero. 51 F G551D/2 62 39.13 16.50 0.42 CFTR-RD CBAVD 41 M W1282X/5T 55 84.61 20.69 20.01 CFTR-RD CBAVD 52 M F508del/R117H (7T) 57 70.39 20.61 20.01 CFTR-RD CBAVD 41 M F508del/5T 40 68.00 22.29 20.03 CFTR-RD CBAVD 47 M G551D/R117H (7T) 57 65.93 10.08 0.15 CFTR-RD CBAVD 40 M L206W/W216C 42 67.80 17.00 0.25 CFTR-RD CBAVD 26 M 36599delC15T/7T 55 91.55 0.18 0.00 CFTR-RD Sinopulm 65 F F508del/c.876-9_876-6delGATT 51 74.30 32.20 0.43 CFTR-RD Sinopulm 39 F R764X/2 12 24.64 3.49 0.14 CFTR-RD Sinopulm 17 F 5T/2 50 52.95 14.24 0.27 CFPS 21 M F508del/2 97 46.19 0.56 0.01 CFPS 33 M F508del/3849110kbC.T 50 76.22 22.94 20.04 CFPS 58 M 71111G.T/A455E 72 70.19 23.06 20.04 CFPS 41 M G551D/3849110kbC.T 88 87.37 0.08 0.00 CFPS 54 F F508del/R117C 59 36.74 1.06 0.03 CFPS 23 F F508del/A455E 82 64.85 3.46 0.05 CFPS 30 F D1152H/D1152H 31 41.52 23.54 20.09 CFPS 55 F G551D/2 99 67.62 21.78 20.03 CFPS 42 F F508del/1002-2A.G 94 27.64 2.63 0.10 CFPS 46 F 3849110kbC.T/3849110kbC.T 53 24.43 21.16 20.05 CFPS 14 F R1162X/3849110kbC.T 46 50.19 20.49 20.01 CFPI 32 M F508del/F508del 108 73.93 1.41 0.02 CFPI 28 M F508del/F508del 84 95.13 3.45 0.04 CFPI 24 F F508del/F508del 109 60.48 4.06 0.07 CFPI 34 F F508del/F508del 115 79.24 0.99 0.01 CFPI 35 F F508del/F508del 87 79.79 23.02 20.04 CFPI 44 F F508del/F508del 112 80.60 1.23 0.02 CFPI 23 F F508del/G551D 90 45.80 0.80 0.02 Definition of abbreviations: CBAVD &#bc; congenital bilateral absence of vas deference; CF &#bc; cystic fibrosis; CFPI &#bc; pancreatic-insufficient patients with CF; CFPS &#bc; pancreatic-sufficient patients with CF; CFTR &#bc; CF transmembrane regulator; CFTR-RD &#bc; CFTR-related disorder; hetero &#bc; heterozygotes; sinopulm &#bc; chronic sinopulmonary disease. Login to comment 82 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Leu206Trp ABCC7 p.Arg764* ABCC7 p.Trp216Cys Four men with congenital bilateral absence of vas deference (CBAVD) (W1282X/5T, F508del/R117H [7T], F508del/5T, and 36599delC17T/5T) showed no b-adrenergic secretory response; one woman with chronic sinopulmonary disease (F508del/c.876-9_876-6delGATT) responded comparably with heterozygotes; two men with CBAVD (G551D/ R117H and L206W/W216C) and two women with chronic sinopulmonary disease (5T/2 and R764X/2) demonstrated b-adrenergic sweat secretion that was reduced compared with heterozygotes (Figure 3A, Table 1). Login to comment 83 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Leu206Trp ABCC7 p.Arg764* ABCC7 p.Trp216Cys Four men with congenital bilateral absence of vas deference (CBAVD) (W1282X/5T, F508del/R117H [7T], F508del/5T, and 36599delC17T/5T) showed no b-adrenergic secretory response; one woman with chronic sinopulmonary disease (F508del/c.876-9_876-6delGATT) responded comparably with heterozygotes; two men with CBAVD (G551D/ R117H and L206W/W216C) and two women with chronic sinopulmonary disease (5T/2 and R764X/2) demonstrated b-adrenergic sweat secretion that was reduced compared with heterozygotes (Figure 3A, Table 1). Login to comment 92 ABCC7 p.Asp1152His ABCC7 p.Arg117Cys Of note, four of these patients with CFPS carrying 3849110kbC.T or D1152H on one or two alleles had sweat chloride results between 31 and 52 mmol/L, whereas one subject with CFPS carried F508del/R117C with sweat [Cl2 ] 59 mmol/L. Login to comment 93 ABCC7 p.Asp1152His ABCC7 p.Arg117Cys Of note, four of these patients with CFPS carrying 3849110kbC.T or D1152H on one or two alleles had sweat chloride results between 31 and 52 mmol/L, whereas one subject with CFPS carried F508del/R117C with sweat [Cl2 ] 59 mmol/L. Login to comment 145 ABCC7 p.Asp1152His In addition, b-adrenergic sweat test confirmed CF disease in individuals carrying mutations (e.g., 3849110kBC.T and D1152H) that commonly exhibit normal or borderline sweat [Cl2 ] (23, 24). Login to comment 146 ABCC7 p.Asp1152His In addition, b-adrenergic sweat test confirmed CF disease in individuals carrying mutations (e.g., 3849110kBC.T and D1152H) that commonly exhibit normal or borderline sweat [Cl2 ] (23, 24). Login to comment